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GSE35972
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Using the NCI anticancer drug screen data, we identified two compounds from the thiosemicarbazone family that manifest increased growth inhibitory activity in mutant p53 cells, particularly for the p53R175 mutant. Mechanistic studies reveal that NSC319726 restores WT structure and function to the p53R175 mutant. This compound kills p53R172H knock-in mice with extensive apoptosis and inhibits xenograft tumor growth in a 175-allele specific mutant p53 dependent manner. This activity depends upon the zinc ion chelating properties of the compound as well as redox changes. These data identify NSC319726 as a p53R175 mutant reactivator and as a lead compound for p53 targeted drug development.
Publication Title
Allele-specific p53 mutant reactivation.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Estrogen-Related Receptor alpha (ERR) is a nuclear receptor that acts principally as a regulator of metabolism processes particularly in tissues subjected to high-energy demand. Besides its implication in energy metabolism and mitochondrial biogenesis, ERR was recently associated with tumorigenesis. Notably, increased expression of ERR was noted in different cancerous tissues as breast, ovary and colon. However, supplemental studies are required to better understand the role of ERR in colon carcinoma.
Publication Title
ERRα metabolic nuclear receptor controls growth of colon cancer cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Treatment with Aurora inhibitors has been shown to induce diverse biological responses in different tumor cell lines, in part depending on their p53 status. To characterize at the transcriptional level the effects of Danusertib we analyzed by microarray different tumor cell lines, with WT or mutant p53 status, that showed differential cell cycle response upon drug treatment.
Publication Title
Transcriptional analysis of the Aurora inhibitor Danusertib leading to biomarker identification in TP53 wild type cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Rattus norvegicus
- 9 Downloadable Samples
NextSeq 500
Description
Zinc (Zn2+) is an integral component of many proteins and has been shown to act in a regulatory capacity in different mammalian systems, including as a neurotransmitter in neurons throughout the brain. While Zn2+ plays an important role in modulating neuronal potentiation and synaptic plasticity, little is known about the signaling mechanisms of this regulation. In dissociated rat hippocampal neuron cultures, we used fluorescent Zn2+ sensors to rigorously define resting Zn2+ levels and stimulation-dependent intracellular Zn2+ dynamics, and we performed RNA-Seq to characterize Zn2+-dependent transcriptional effects upon stimulation. We found that relatively small changes in cytosolic Zn2+ during stimulation altered expression levels of 931 genes, and these Zn2+ dynamics induced transcription of many genes implicated in neurite expansion and synaptic growth. Additionally, while we were unable to verify the presence of synaptic Zn2+ in these cultures, we did detect the synaptic vesicle Zn2+ transporter ZnT3 and found it to be substantially upregulated by cytosolic Zn2+ increases. These results provide the first global sequencing-based examination of Zn2+-dependent changes in transcription and identify genes that may mediate Zn2+-dependent processes and functions. Overall design: 3 replicates of each of 3 conditions (KCl treatment, KCl/Zn treatment, KCl/TPA treatment), none of which are control conditions. KCl treatment was used as the reference condition for all comparisons. TPA = tris(2-pyridylmethyl)amine, a Zn2+ chelator.
Publication Title
Intracellular Zn<sup>2+</sup> transients modulate global gene expression in dissociated rat hippocampal neurons.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 40 Downloadable Samples
- Illumina HiSeq 2000, Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Critical role for TRIM28 and HP1b/g in the epigenetic control of T cell metabolic reprogramming and effector differentiation
Publication Title
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Critical role for TRIM28 and HP1b/g in the epigenetic control of T cell metabolic reprogramming and effector differentiation
Publication Title
Critical role for TRIM28 and HP1β/γ in the epigenetic control of T cell metabolic reprograming and effector differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 1 Downloadable Sample
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/-mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/-mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/-mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/-and double mutant Axin2-/-:Runx2+/-mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/-mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/-mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation.
Publication Title
Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Histone deacetylase inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, these drugs inhibit multiple Hdacs and have detrimental effects on the pre- and post-natal skeleton. To better understand how Hdac inhibitors affect the skeleton, we focused on understanding the role of one of their targets, Hdac3, in endochondral bone formation by deleting it in immature murine chondrocyte micro masses with Adeno-Cre. Hdac3-deficient chondrocytes expressed higher levels of pro-inflammatory and matrix degrading genes (e.g., Il-6, Mmp3, Mmp13, Saa3) and lower levels of genes related to the extracellular matrix production, bone development and ossification (e.g., Acan, Col2a1, Ihh, Col10a1). Histone acetylation was increased in and around genes with elevated expression. Overall design: High Throughput RNA sequencing and Chromatin immunopreciptation sequencing experiments were performed in chondrocyte cultures. Differential analysis was conducted on ChIP-seq and RNA-seq data to identify H3K27Ac profile for up and down regulated genes in Hdac3-deficient murine chondrocytes.
Publication Title
Histone deacetylase 3 supports endochondral bone formation by controlling cytokine signaling and matrix remodeling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples